A quantitative pressure and microbubble-size dependence study of focused ultrasound-induced blood-brain barrier opening reversibility in vivo using MRI

Magn Reson Med. 2012 Mar;67(3):769-77. doi: 10.1002/mrm.23063. Epub 2011 Aug 19.

Abstract

Focused ultrasound in conjunction with the systemic administration of microbubbles has been shown to open the blood-brain barrier (BBB) selectively, noninvasively and reversibly. In this study, we investigate the dependence of the BBB opening's reversibility on the peak-rarefactional pressure (0.30-0.60 MPa) as well as the microbubble size (diameters of 1-2, 4-5, or 6-8 μm) in mice using contrast-enhanced T(1)-weighted (CE-T(1)) MR images (9.4 T). Volumetric measurements of the diffusion of Gd-DTPA-BMA into the brain parenchyma were used for the quantification of the BBB-opened region on the day of sonication and up to 5 days thereafter. The volume of opening was found to increase with both pressure and microbubble diameter. The duration required for closing was found to be proportional to the volume of opening on the day of opening, and ranged from 24 h, for the smaller microbubbles, to 5 days at high peak-rarefactional pressures. Overall, larger bubbles did not show significant differences. Also, the extent of BBB opening decreased radially towards the focal region until the BBB's integrity was restored. In the cases where histological damage was detected, it was found to be highly correlated with hyperintensity on the precontrast T(1) images.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blood-Brain Barrier / diagnostic imaging*
  • Blood-Brain Barrier / metabolism*
  • Contrast Media / pharmacokinetics*
  • Gadolinium DTPA / pharmacokinetics*
  • Image Processing, Computer-Assisted
  • Longitudinal Studies
  • Magnetic Resonance Imaging / methods
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microbubbles
  • Permeability
  • Pressure
  • Transducers
  • Ultrasonics / instrumentation*
  • Ultrasonography

Substances

  • Contrast Media
  • gadodiamide
  • Gadolinium DTPA